The complement system in renal homograft recipients

The whole serum complement and its components were studied in 24 recipients of 27 renal homografts. In 12 of 13 instances in which homograft rejection was diagnosed, it was accompanied by significant declines in CH50, IA50, C4, and C3 levels, and to a lesser degree in C1 and C2 levels. Fourteen patients had normal graft function during the postoperative course of study, and in 13 of the 14 the complement levels were within the normal range throughout. In two recipients with systemic lupus erythematosus, very low initial complement levels increased to normal levels following removal of the native kidneys, splenectomy, and the provision of a well-functioning homograft. Anticomplement activity and elevated titers of C1 and C3 inactivators were observed in some patients, but these did not correlate with the changes in CH50. The findings confirm that the complement system participates in renal homograft rejection. © 1972

Acute pancreatitis and hyperamylasemia in renal homograft recipients.

In a series of 301 renal homograft recipients, 17 (5.6%) had acute pancreatitis at some time after transplantation. Eleven of these patients died, for a mortality of 64.7%. In each instance, pancreatitis was a major factor in a complex chain of lethal events to which immunosuppression invariably contributed. An additional 43 patients (14.3%) developed asymptomatic hyperamylasemia after transplantation and, undoubtedly, some of these recipients also had pancreatitis. The factors causing pancreatitis in the renal transplantation patient include uremia, hyperparathyroidism, pancreatic injury by drugs, infections resulting from chronic immunosuppression, gallstones, and operative trauma to the pancreas. In cases of preexisting pancreatitis, transplantation is not necessarily precluded, but efforts should be made to find a specific cause of the pancreatitis and take corrective measures, such as biliary tract surgery or parathyroidectomy if indicated, in advance of transplantation

Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes : Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration

Background: The potential for global collaborations to better inform public health policy regarding major non-hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. Methods: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. Conclusions: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients. (C) 2016 Elsevier Ireland Ltd.Peer reviewe

Externalizing, internalizing and fostering commitment: the case of born-global firms in emerging economies

This paper examines the HR practices of mature born-global firms from twenty-nine emerging economies. Through an examination of large scale survey data the paper questions the extent to which firm size impacts the employment of temporary workers, the employment of skilled workers and the extent of employee training. Findings suggest that as firm size increases the use of temporary workers decreases, the number of skilled workers increases and the number of employees receiving training also increases. The paper highlights how born-global firms are able to shift away from externalized, market-based approaches towards more internalized, commitment-based approaches in order to survive, adapt and grow

Idiopathic sclerosing mesenteritis in paediatrics: Report of a successfully treated case and a review of literature

A 6 year old female with symptoms of small bowel obstruction underwent an exploratory laparotomy which revealed widespread evidence of inflammatory fibrotic adhesions involving the jejunal mesentery. In view of persistent growth failure, chronic anaemia, elevated acute phase reactants and imaging evidence of a diffuse progressive inflammatory process, the child was treated with corticosteroids and methotrexate with complete response. The literature on juvenile idiopathic sclerosing mesenteritis has been reviewed

Effects of Crystalline Anisotropy and Indenter Size on Nanoindentation by Multiscale Simulation

Nanoindentation processes in single crystal Ag thin film under different crystallographic orientations and various indenter widths are simulated by the quasicontinuum method. The nanoindentation deformation processes under influences of crystalline anisotropy and indenter size are investigated about hardness, load distribution, critical load for first dislocation emission and strain energy under the indenter. The simulation results are compared with previous experimental results and Rice-Thomson (R-T) dislocation model solution. It is shown that entirely different dislocation activities are presented under the effect of crystalline anisotropy during nanoindentation. The sharp load drops in the load–displacement curves are caused by the different dislocation activities. Both crystalline anisotropy and indenter size are found to have distinct effect on hardness, contact stress distribution, critical load for first dislocation emission and strain energy under the indenter. The above quantities are decreased at the indenter into Ag thin film along the crystal orientation with more favorable slip directions that easy trigger slip systems; whereas those will increase at the indenter into Ag thin film along the crystal orientation with less or without favorable slip directions that hard trigger slip systems. The results are shown to be in good agreement with experimental results and R-T dislocation model solution

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

BACKGROUND: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. METHODS: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. FINDINGS: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. INTERPRETATION: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 21% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 130 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (188%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (502%) of 11 476 included individuals were female and 5720 (498%) were male. Sex data were missing for 372 (31%) of 11 848 individuals. Median age at registry entry was 96 years (IQR 58-132). 10 099 (899%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (101%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (52%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [924%] of 10 202) than in children and adolescents from non-high-income countries (199 [480%] of 415). 3414 (316%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (724%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 500 mmol/L (IQR 405-608). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation.Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Recent D-T results on TFTR

Routine tritium operation in TFTR has permitted investigations of alpha particle physics in parameter ranges resembling those of a reactor core. ICRF wave physics in a DT plasma and the influence of isotopic mass on supershot confinement have also been studied. Continued progress has been made in optimizing fusion power production in TFTR, using extended machine capability and Li wall conditioning. Performance is currently limited by MHD stability. A new reversed magnetic shear regime is being investigated with reduced core transport and a higher predicted stability limit